Micro-pumps, generally defined as handling fluid volume on the order of 1 milliliter and below, have wide applications in chemical, biological and medical systems, particularly related to precision medicine in the past decades. Among the first micro-pumps, Smits (Reference [1]) used them in controlled insulin delivery systems for maintaining diabetics' blood sugar levels without frequent needle injections. Recently, micro-pumps are used to dispense engineered macromolecules into tumors or the bloodstream to destroy cancer cells. The most well-known application of micro-pumps might be the ink-jet printheads developed in the 1970s by IBM (Reference [2]), which are still widely used today. A micro scale chamber made from piezoelectric material are made to contract by the application of an electric charge. As the chamber contracts, ink contained in it is forced out through the nozzle as a droplet. As the chamber returns to its original state, capillary action causes ink to flow into the chamber from the ink supply, making it ready to produce the next drop.
Micro-pumps, or pumps in general, are divided into two major categories: displacement pumps, which exert pressure on the working fluid through moving boundaries, and dynamic pumps, which continuously add energy to the working fluid. Smits' insulin delivery pump and the ink-jet printhead belong to the first category, while the common centrifugal pumps, and the latest eletrohydodynamic pumps are in the second one.
There are some major drawbacks of the existing micro-pumps. The major one is the complexity of the actuation mechanism and the micro-valves. These micro-pumps are hard to fabricate in micro scale and they have moving parts which are subject to mechanical failure, wearing, stress and fatigue. Such delicate parts also prevent their true miniaturization. For example, piezoelectric micro-pump could not be made less than the size of its piezoelectric disks which is around 10 mm. Reliability, power consumption, cost and biocompatibility are the critical factors in developing implantable micro-pumps. The deficiencies in these areas have precluded widespread implantation of micro-pumps.
Recent developments in the microfluidic market has drawn out more and more new micro-pump designs from both industry and academia. Micro bubble pumps are among the fastest developing categories. One type of micro bubble pump is the thermal-bubble-actuated micro-pump, which is based on thermopneumatic actuation. Prosperetti's micro-pump (Reference [3]) consists of a resistive heater arranged in a conical-shaped chamber connecting two liquid reservoirs. The actuation mechanism comes from periodically nucleating and collapsing thermal bubbles within the conical-shaped chamber. Zimmermann et al. (Reference [4]) designed a planar micro-pump which could be easily integrated into micro systems. This micro-pump comprises of heat resistors for generation of vapor bubbles and two in-plane flap valves for flow control. Similarly, cyclic pulsing of the resistive heaters causes bubbles to grow and collapse in the bubble chamber, which provides the pumping action. Although thermal bubbles can be easily generated even if the pump is small, heat loss and residual bubbles can decrease the flow rate significantly.
Besides thermal-bubble-actuated micro-pumps, micro bubble pumps utilizing electrochemical energy have also been developed. Kabata et al. (Reference [5]) proposed a prototype micro-pump for insulin administration. Hydrogen bubbles are generated through electrolysis of water in a closed chamber when electric current is present in the water, exerting pressure on the insulin solution through a silicone rubber diaphragm separating the two liquids. In Kabata's design, electric current is produced through oxidation of a silver anode. The electrochemically driven microwell drug delivery device reported by Chung et al. (Reference [6]) applies a similar mechanism. Instead of oxidizing silver anode, Chung et al.'s device produces an electric current by dissolution of a gold membrane. For this type of micro bubble pump, no external energy supply is needed and the chemical reactions provide fast drug delivery. However, actuation based on electrochemical energy has issues in the continuous supply of materials and their compatibility with microfluidics or in vivo environments.
Recently, micro-propulsion of oscillating bubbles through excitation of external acoustic waves has drawn the attention of many scientists as an alternative actuation mechanism. The advantage of acoustic energy is that it can act on the bubble remotely from an outside source so that the micro-pump does not need internal energy to function. This feature is critically important in biomedical applications and drug delivery as it is non-invasive and greatly simplifies the design of the bubble pump. Dijkink et al. (Reference [7]) built an acoustic bubble propulsion device called the “acoustic scallop”, consisting of a small tube immersed in liquid and closed at one end with a bubble trapped inside. The bubble oscillations generate a quasi-steady streaming flow that eventually produces propulsion forces in the device. Feng et al. (Reference [8]) reported a micro-propulsion-based underwater micros-swimmer for navigating microfluidic environments and possibly narrow passages in the human body to perform drug delivery and other tasks.
The present invention aims an implantable, non-invasive, compact and biocompatible device for drug delivery and biomedical applications.